1. Field of The Invention
The invention concerns a method for synthesizing gem-difluorinated C-glycopeptide compounds. It applies in particular, but not exclusively, to the preparation of compounds or compositions usable notably in the preservation of biological materials and in cryosurgery.
2. Description of The Prior Art
Antifreeze biological compounds exist in the natural environment, glycoproteins in particular. These are compounds present for example in some fishes, enabling them to survive in a low-temperature environment, i.e. near zero or sub-zero temperatures.
Also, it is known that when water freezes, this phenomenon is accompanied by a volume increase due to the three-dimensional growth of ice.
This increase, and resulting osmosis, cause serious damage in living tissues: cell membranes are ruptured, blood ceases to flow and cell microstructures are disturbed.
For many years, scientists have been investigating how antifreeze compounds taken from the natural environment (fish, amphibians, plants, insects . . . ) have an influence on these phenomena, these compounds being notably proteins and glycoproteins.
Intensive research is focusing on the synthesis of similar compounds that are sufficiently stable and whose activity is at least equal to or even greater than the activity of the natural molecules, for commercial applications.
Due to the presence of an osidic bond (bond involving oxygen said to be in an anomeric position) glycoproteins are fragile relatively to several enzymatic systems, including glycosidase enzymes, and are also sensitive to acid-base hydrolysis making their synthesis more difficult.
It is therefore of interest, in order to allow these compounds to maintain their biological properties, to replace the oxygen in the osidic bond so that this bond is no longer deteriorated by an enzymatic process.
Analogs, in which oxygen is replaced by a CH2 group, have been synthesized, but despite an increase in stability and a steric hindrance similar to that of oxygen, the CH2 group has not always proved to be a good mimic of osidic oxygen. Consequently, the biological properties of the initial compound are not always found.
Other classes of compounds in which oxygen is replaced by a nitrogen or sulphur and more recently by a difluoromethylene group are being researched with a view to imparting increased stability to glycoconjugate compounds in a biological medium.
The CF2 group shows particular resistance to processes of biochemical degradation and therefore allows the synthesis of non-hydrolysable structures.
This O/CF2 transposition seems to be especially well adapted to mimicking oxygen at electronic level; the two fluorine atoms acting as the two oxygen-free doublets.
Said compounds could possibly be used for numerous applications such as the preservation of cells, blood platelets, tissues, organs, or for cryosurgery.
There exists a strong demand for an improvement in the storage and preservation of irreplaceable living cells, including sperm, ovules and embryos so that they undergo much less damage than with methods currently used.
The term preservation generally includes preservation at different temperatures, including cryopreservation down to temperatures as low as −196° C.
Therefore, compounds used as adjuvants for preservation and having good stability could be useful for preserving biological materials, notably:                for storing whole human organs such as kidneys, hearts and livers to be transplanted under no time constraints,        for preserving delicate tissues with minimum damage and for a sufficiently long period to allow optionally international distribution,        for preserving blood platelets and cells,        for protecting certain organisms, bacteria, viruses or vaccines.        
Cryosurgery, also called cryotherapy, is the use of extreme cold produced by liquid nitrogen (or argon gas) to destroy abnormal tissues.
It is used to treat external tumours such as skin tumours but is also used to treat tumours inside the body, notably in the prostate and liver. Researchers have tested cryosurgery as a treatment for a certain number of cancers including breast cancer, colon and kidney cancers.
In addition, some studies have reported that at a certain concentration (5-10 mg/ml), antifreeze glycoproteins and proteins produce spicule-shaped ice crystals which increase the probability of cell rupture and death during freezing. This property of ice crystals modified by antifreeze glycoproteins and proteins finds applications of high interest in the treatment of some cancers, if they are used in conjunction with cryosurgery.